ArticleCell death and differentiation2023
Targeting HDAC3 to overcome the resistance to ATRA or arsenic in acute promyelocytic leukemia through ubiquitination and degradation of PML-RARα.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- CXCR2 blockade potentiates HDAC3 deletion mediated antitumor immunity in colorectal cancer.Cell death & disease · 2026Article
- Spatiotemporal Sequential Delivery of Chidamide Regulates Macrophage Reprogramming in Lymphoma Microenvironment Through HDACs-STAT3 Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The impactful role of the HDACs in the regulation of gene expression and as targets for disease therapy.Science advances · 2026Review
- Upregulation of GnT-IVa and Its Critical Roles in ATRA-Induced Differentiation of Acute Promyelocytic Leukemia Cells.Biomolecules · 2026Article
- Histone deacetylases: Function in tumor development and therapeutic prospects (Review).Oncology letters · 2026Review
- Arsenic Sulfide Induces Apoptosis in Myelodysplastic Neoplasm Cells Through the Suppression of ABI2.Biological procedures online · 2025Article
- PDCD4: A critical regulator in leukemic signaling networks and its therapeutic potential.Molecular biology reports · 2025Review
- Article
- Targeting USP2 induces degradation of PML-RARα with or without drug-resistant mutations in acute promyelocytic leukemia.Acta biochimica et biophysica Sinica · 2025Article
- HDAC3-YY1-RAB5A axis remodels AML-supportive niche by modulating mitochondrial homeostasis in bone marrow stromal cells.Cell death & disease · 2025Article
- The Role of HDAC3 in Pulmonary Diseases.Lung · 2025Review
- Review
- CPSF6-RARγ interacts with histone deacetylase 3 to promote myeloid transformation in RARG-fusion acute myeloid leukemia.Nature communications · 2025Article
- Exosomal circ_0006896 promotes AML progression via interaction with HDAC1 and restriction of antitumor immunity.Molecular cancer · 2025Article
- SUMOylation involved in malignant progression of multiple tumors and SENP5 may improve the chemotherapy sensitivity of hypoxic tumors.Frontiers in pharmacology · 2025Article
- Advances in the application of patient-derived xenograft models in acute leukemia resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Periplocin Targets HDAC10 to Inhibit NF-κB Signaling and Induce Apoptosis in Myeloid Leukemia Cells.Journal of Cancer · 2025Article
- Epigenetic mechanisms of drug resistance in acute myeloid leukemia: advances in small-molecule targeted therapy.Frontiers in pharmacology · 2025Review
- Recent advancements in biomarkers, therapeutics, and associated challenges in acute myeloid leukemia.Annals of hematology · 2024Review
- 20(S)-ginsenoside Rh2 ameliorates ATRA resistance in APL by modulating lactylation-driven METTL3.Journal of ginseng research · 2024Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute promyelocytic leukemia (APL) is driven by the oncoprotein PML-RARα, which recruits corepressor complexes, including histone deacetylases (HDACs), to suppress cell differentiation and promote APL initiation. All-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) or chemotherapy highly improves the prognosis of APL patients. However, refractoriness to ATRA and ATO may occur, which leads to relapsed disease in a group of patients. Here, we report that HDAC3 was highly expressed in the APL subtype of AML, and the protein level of HDAC3 was positively associated with PML-RARα. Mechanistically, we found that HDAC3 deacetylated PML-RARα at lysine 394, which reduced PIAS1-mediated PML-RARα SUMOylation and subsequent RNF4-induced ubiquitylation. HDAC3 inhibition promoted PML-RARα ubiquitylation and degradation and reduced the expression of PML-RARα in both wild-type and ATRA- or ATO-resistant APL cells. Furthermore, genetic or pharmacological inhibition of HDAC3 induced differentiation, apoptosis, and decreased cellular self-renewal of APL cells, including primary leukemia cells from patients with resistant APL. Using both cell line- and patient-derived xenograft models, we demonstrated that treatment with an HDAC3 inhibitor or combination of ATRA/ATO reduced APL progression. In conclusion, our study identifies the role of HDAC3 as a positive regulator of the PML-RARα oncoprotein by deacetylating PML-RARα and suggests that targeting HDAC3 could be a promising strategy to treat relapsed/refractory APL.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.